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https://www.readbyqxmd.com/read/28429768/reassembling-embryos-in-vitro-from-component-stem-cells
#1
Caroline Kubaczka, George Q Daley
Researchers at the University of Cambridge, UK have succeeded in reconstructing mouse embryos by combining pluripotent embryonic and multipotent trophoblast stem cells in a 3D scaffold; the study from the laboratory of Professor Zernicka-Goetz, recently published in Science, provides a break-through tool to probe early mammalian development outside the uterus. Achieving a similar feat with human cells might necessitate reconsideration of the 14-day rule as a limitation of such research.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28394331/dectin-1-activation-on-macrophages-by-galectin-9-promotes-pancreatic-carcinoma-and-peritumoral-immune-tolerance
#2
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Atsuo Ochi, Daniel W Heindel, Ki Buom Lee, Constantinos P Zambirinis, Gautam Sd Balasubramania Pandian, Shivraj Savadkar, Alejandro Torres-Hernandez, Shruti Nayak, Ding Wang, Mautin Hundeyin, Brian Diskin, Berk Aykut, Gregor Werba, Rocky M Barilla, Robert Rodriguez, Steven Chang, Lawrence Gardner, Lara K Mahal, Beatrix Ueberheide, George Miller
The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined. Furthermore, non-pathogen-derived ligands for dectin 1 have not been characterized. We found that dectin 1 is highly expressed on macrophages in pancreatic ductal adenocarcinoma (PDA)...
April 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28350984/autophagy-it-s-in-your-blood
#3
Sergei Doulatov, George Q Daley
Autophagy, a central pathway for cellular homeostasis, plays diverse roles in development, cancer, aging, and neurodegeneration. In a new report in Nature, Ho et al. (2017) show that autophagy is essential for maintaining the replicative quiescence of hematopoietic stem cells throughout life by limiting the number of active mitochondria.
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28345379/the-role-of-%C3%AE-%C3%AE-t-cells-in-pancreatic-cancer-what-could-this-mean-for-the-clinic
#4
Donnele Daley, George Miller
Pancreatic cancer is a devastating disease where the 5-year survival is less that 10%. Recent studies have shown that ?? T cells are a dominant lymphocyte subset in pancreatic cancer and they promote the progression of the disease. With the emerging use of T cell- based therapy for cancer, ?? T cells are an attractive target for novel immunotherapy in pancreatic cancer.
March 26, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28296612/polar-extremes-in-the-clinical-use-of-stem-cells
#5
George Q Daley
The U.S. biotechnology and pharmaceutical industries arguably lead the world in innovation while operating under stringent regulations set by the Food and Drug Administration (FDA). Although flexible pathways exist to accelerate the development or approval of treatments for serious illnesses or..
March 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28272977/signaling-through-rna-binding-proteins-as-a-cell-fate-regulatory-mechanism
#6
Kaloyan M Tsanov, George Q Daley
No abstract text is available yet for this article.
April 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28179501/drug-discovery-for-diamond-blackfan-anemia-using-reprogrammed-hematopoietic-progenitors
#7
Sergei Doulatov, Linda T Vo, Elizabeth R Macari, Lara Wahlster, Melissa A Kinney, Alison M Taylor, Jessica Barragan, Manav Gupta, Katherine McGrath, Hsiang-Ying Lee, Jessica M Humphries, Alex DeVine, Anupama Narla, Blanche P Alter, Alan H Beggs, Suneet Agarwal, Benjamin L Ebert, Hanna T Gazda, Harvey F Lodish, Colin A Sieff, Thorsten M Schlaeger, Leonard I Zon, George Q Daley
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients...
February 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077678/disruptive-reproductive-technologies
#8
REVIEW
I Glenn Cohen, George Q Daley, Eli Y Adashi
In vitro gametogenesis raises new possibilities for reproductive and regenerative medicine as well as vexing policy challenges.
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28009288/engineered-murine-hscs-reconstitute-multi-lineage-hematopoiesis-and-adaptive-immunity
#9
Yi-Fen Lu, Patrick Cahan, Samantha Ross, Julie Sahalie, Patricia M Sousa, Brandon K Hadland, Wenqing Cai, Erik Serrao, Alan N Engelman, Irwin D Bernstein, George Q Daley
Hematopoietic stem cell (HSC) transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs) could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27992407/lin28-phosphorylation-by-mapk-erk-couples-signalling-to-the-post-transcriptional-control-of%C3%A2-pluripotency
#10
Kaloyan M Tsanov, Daniel S Pearson, Zhaoting Wu, Areum Han, Robinson Triboulet, Marc T Seligson, John T Powers, Jihan K Osborne, Susan Kane, Steven P Gygi, Richard I Gregory, George Q Daley
Signalling and post-transcriptional gene control are both critical for the regulation of pluripotency, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein, has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA biogenesis and direct modulation of mRNA translation. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells, which increases its levels via post-translational stabilization...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27974805/stem-cells-valine-starvation-leads-to-a-hungry-niche
#11
COMMENT
R Grant Rowe, George Q Daley
No abstract text is available yet for this article.
January 12, 2017: Nature
https://www.readbyqxmd.com/read/27777239/tgf-%C3%AE-inhibitors-stimulate-red-blood-cell-production-by-enhancing-self-renewal-of-bfu-e-erythroid-progenitors
#12
Xiaofei Gao, Hsiang-Ying Lee, Edroaldo Lummertz da Rocha, Cheng Zhang, Yi-Fen Lu, Dandan Li, Yuxiong Feng, Jideofor Ezike, Russell R Elmes, M Inmaculada Barrasa, Patrick Cahan, Hu Li, George Q Daley, Harvey F Lodish
Burst-forming unit erythroid progenitors (BFU-Es) are so named based on their ability to generate in methylcellulose culture large colonies of erythroid cells that consist of "bursts" of smaller erythroid colonies derived from the later colony-forming unit erythroid progenitor erythropoietin (Epo)-dependent progenitors. "Early" BFU-E cells forming large BFU-E colonies presumably have higher capacities for self-renewal than do "late" BFU-Es forming small colonies, but the mechanism underlying this heterogeneity remains unknown...
December 8, 2016: Blood
https://www.readbyqxmd.com/read/27723718/progress-towards-generation-of-human-haematopoietic-stem-cells
#13
Lara Wahlster, George Q Daley
De novo generation of haematopoietic stem cells from different human pluripotent stem cell sources remains a high priority for haematology and regenerative medicine. At present, efficient derivation of functional haematopoietic stem cells with the capability for definitive in vivo engraftment and multi-lineage potential remains challenging. Here, we discuss recent progress and strategies to overcome obstacles that have thwarted past efforts. In addition, we review promising advances in the generation of mature blood lineages and the potential of induced pluripotent stem cells...
November 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27705794/developmental-vitamin-d-availability-impacts-hematopoietic-stem-cell-production
#14
Mauricio Cortes, Michael J Chen, David L Stachura, Sarah Y Liu, Wanda Kwan, Francis Wright, Linda T Vo, Lindsay N Theodore, Virginie Esain, Isaura M Frost, Thorsten M Schlaeger, Wolfram Goessling, George Q Daley, Trista E North
Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including pregnant women and children. Despite its high incidence, the impact of active vitamin D3 (1,25(OH)D3) on embryonic development beyond osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OH)D3 availability modulates zebrafish hematopoietic stem and progenitor cell (HSPC) production. Loss of Cyp27b1-mediated biosynthesis or vitamin D receptor (VDR) function by gene knockdown resulted in significantly reduced runx1 expression and Flk1(+)cMyb(+) HSPC numbers...
October 4, 2016: Cell Reports
https://www.readbyqxmd.com/read/27569912/%C3%AE-%C3%AE-t-cells-support-pancreatic-oncogenesis-by-restraining-%C3%AE-%C3%AE-t-cell-activation
#15
Donnele Daley, Constantinos Pantelis Zambirinis, Lena Seifert, Neha Akkad, Navyatha Mohan, Gregor Werba, Rocky Barilla, Alejandro Torres-Hernandez, Mautin Hundeyin, Vishnu Raj Kumar Mani, Antonina Avanzi, Daniel Tippens, Rajkishen Narayanan, Jung-Eun Jang, Elliot Newman, Venu Gopal Pillarisetty, Michael Loran Dustin, Dafna Bar-Sagi, Cristina Hajdu, George Miller
Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αβT cells. Although αβT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation...
September 8, 2016: Cell
https://www.readbyqxmd.com/read/27559045/mincle-signaling-promotes-con-a-hepatitis
#16
Stephanie H Greco, Alejandro Torres-Hernandez, Aleksandr Kalabin, Clint Whiteman, Rae Rokosh, Sushma Ravirala, Atsuo Ochi, Johana Gutierrez, Muhammad Atif Salyana, Vishnu R Mani, Savitha V Nagaraj, Michael Deutsch, Lena Seifert, Donnele Daley, Rocky Barilla, Mautin Hundeyin, Yuriy Nikifrov, Karla Tejada, Bruce E Gelb, Steven C Katz, George Miller
Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27522134/australian-group-on-antimicrobial-resistance-australian-enterobacteriaceae-sepsis-outcome-programme-annual-report-2014
#17
MULTICENTER STUDY
Jan M Bell, John D Turnidge, Geoffrey W Coombs, Denise A Daley, Thomas Gottlieb, Jenny Robson, Narelle George
The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2014 survey was the second year to focus on blood stream infections. During 2014, 5,798 Enterobacteriaceae species isolates were tested using commercial automated methods (Vitek 2, BioMérieux; Phoenix, BD) and results were analysed using the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2015)...
June 30, 2016: Communicable Diseases Intelligence Quarterly Report
https://www.readbyqxmd.com/read/27430299/a-cross-sectional-study-of-animal-and-human-colonization-with-methicillin-resistant-staphylococcus-aureus-mrsa-in-an-aboriginal-community
#18
Peter Daley, Janak Bajgai, Carla Penney, Karen Williams, Hugh Whitney, George R Golding, Scott Weese
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are common among humans in Aboriginal communities in Canada, for unknown reasons. METHODS: Cross sectional study of humans and dogs in an Aboriginal community of approximately 1200 persons. Our objectives were to measure community-based prevalence of nasal MRSA colonization among humans, use multivariable logistic regression to analyze risk factors for MRSA colonization, and perform molecular typing of Staphylococci isolated to investigate interspecies transmission...
2016: BMC Public Health
https://www.readbyqxmd.com/read/27401346/developmental-regulation-of-myeloerythroid-progenitor-function-by-the-lin28b-let-7-hmga2-axis
#19
R Grant Rowe, Leo D Wang, Silvia Coma, Areum Han, Ronald Mathieu, Daniel S Pearson, Samantha Ross, Patricia Sousa, Phi T Nguyen, Antony Rodriguez, Amy J Wagers, George Q Daley
For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in disease. The hematopoietic system matures from the fetal state, characterized by robust erythrocytic output that supports prenatal growth in the hypoxic intrauterine environment, to the postnatal state wherein granulocytes predominate to provide innate immunity. Regulation of the developmental timing of these myeloerythroid states is not well understood...
July 25, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27383785/multiple-mechanisms-disrupt-the-let-7-microrna-family-in-neuroblastoma
#20
John T Powers, Kaloyan M Tsanov, Daniel S Pearson, Frederik Roels, Catherine S Spina, Richard Ebright, Marc Seligson, Yvanka de Soysa, Patrick Cahan, Jessica Theißen, Ho-Chou Tu, Areum Han, Kyle C Kurek, Grace S LaPier, Jihan K Osborne, Samantha J Ross, Marcella Cesana, James J Collins, Frank Berthold, George Q Daley
Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B...
July 14, 2016: Nature
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